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Delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets

Systemic delivery of conventional chemotherapies can cause negative systemic toxicity, including reduced immunity and damage to organs such as the heart and kidneys—limiting the maximum dose that can be administered. Targeted therapies appear to address this problem by having a specific target while...

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Autores principales: Murphy, Emily M., Centner, Connor S., Bates, Paula J., Malik, Mohammad T., Kopechek, Jonathan A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241745/
https://www.ncbi.nlm.nih.gov/pubmed/32437399
http://dx.doi.org/10.1371/journal.pone.0233466
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author Murphy, Emily M.
Centner, Connor S.
Bates, Paula J.
Malik, Mohammad T.
Kopechek, Jonathan A.
author_facet Murphy, Emily M.
Centner, Connor S.
Bates, Paula J.
Malik, Mohammad T.
Kopechek, Jonathan A.
author_sort Murphy, Emily M.
collection PubMed
description Systemic delivery of conventional chemotherapies can cause negative systemic toxicity, including reduced immunity and damage to organs such as the heart and kidneys—limiting the maximum dose that can be administered. Targeted therapies appear to address this problem by having a specific target while mitigating off-target effects. Biocompatible perfluorocarbon-based nanodroplet emulsions encapsulated by a phospholipid shell are in development for delivery of molecular compounds and hold promise as vehicles for targeted delivery of chemotherapeutics to tumors. When ultrasound is applied, perfluorocarbon will undergo a phase change—ultimately inducing transient perforation of the cell membrane when in close proximity, which is more commonly known as “sonoporation.” Sonoporation allows enhanced intracellular delivery of molecular compounds and will reseal to encapsulate the molecular compound intracellularly. In this study, we investigated delivery of thymoquinone (TQ), a natural hydrophobic phytochemical compound with bioactivity in cancer cells. In addition, we conjugated a G-quadruplex aptamer, ‘AS1411’, to TQ-loaded nanodroplets and explored their effects on multiple human cancer cell lines. AS1411 binds nucleolin, which is over-expressed on the surface of cancer cells, and in addition to its tumor-targeting properties AS1411 has also been shown to induce anti-cancer effects. Thymoquinone was loaded onto AS1411-conjugated nanodroplet emulsion to assess activity against cancer cells. Confocal microscopy indicated uptake of AS1411-conjugated nanodroplets by cancer cells. Furthermore, AS1411-conjugated nanoemulsions loaded with TQ significantly enhanced cytotoxicity in cancer cells compared to free compound. These results demonstrate that AS1411 can be conjugated onto nanodroplet emulsions for targeted delivery to human cancer cells. This novel formulation offers significant potential for targeted delivery of hydrophobic chemotherapeutics to tumors for cancer treatment.
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spelling pubmed-72417452020-06-03 Delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets Murphy, Emily M. Centner, Connor S. Bates, Paula J. Malik, Mohammad T. Kopechek, Jonathan A. PLoS One Research Article Systemic delivery of conventional chemotherapies can cause negative systemic toxicity, including reduced immunity and damage to organs such as the heart and kidneys—limiting the maximum dose that can be administered. Targeted therapies appear to address this problem by having a specific target while mitigating off-target effects. Biocompatible perfluorocarbon-based nanodroplet emulsions encapsulated by a phospholipid shell are in development for delivery of molecular compounds and hold promise as vehicles for targeted delivery of chemotherapeutics to tumors. When ultrasound is applied, perfluorocarbon will undergo a phase change—ultimately inducing transient perforation of the cell membrane when in close proximity, which is more commonly known as “sonoporation.” Sonoporation allows enhanced intracellular delivery of molecular compounds and will reseal to encapsulate the molecular compound intracellularly. In this study, we investigated delivery of thymoquinone (TQ), a natural hydrophobic phytochemical compound with bioactivity in cancer cells. In addition, we conjugated a G-quadruplex aptamer, ‘AS1411’, to TQ-loaded nanodroplets and explored their effects on multiple human cancer cell lines. AS1411 binds nucleolin, which is over-expressed on the surface of cancer cells, and in addition to its tumor-targeting properties AS1411 has also been shown to induce anti-cancer effects. Thymoquinone was loaded onto AS1411-conjugated nanodroplet emulsion to assess activity against cancer cells. Confocal microscopy indicated uptake of AS1411-conjugated nanodroplets by cancer cells. Furthermore, AS1411-conjugated nanoemulsions loaded with TQ significantly enhanced cytotoxicity in cancer cells compared to free compound. These results demonstrate that AS1411 can be conjugated onto nanodroplet emulsions for targeted delivery to human cancer cells. This novel formulation offers significant potential for targeted delivery of hydrophobic chemotherapeutics to tumors for cancer treatment. Public Library of Science 2020-05-21 /pmc/articles/PMC7241745/ /pubmed/32437399 http://dx.doi.org/10.1371/journal.pone.0233466 Text en © 2020 Murphy et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Murphy, Emily M.
Centner, Connor S.
Bates, Paula J.
Malik, Mohammad T.
Kopechek, Jonathan A.
Delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets
title Delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets
title_full Delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets
title_fullStr Delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets
title_full_unstemmed Delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets
title_short Delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets
title_sort delivery of thymoquinone to cancer cells with as1411-conjugated nanodroplets
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241745/
https://www.ncbi.nlm.nih.gov/pubmed/32437399
http://dx.doi.org/10.1371/journal.pone.0233466
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